Allergic airway inflammation and susceptibility to pneumococcal pneumonia in a murine model with real-timein vivoevaluation

Abstract

SummaryThe relationship between allergic airway inflammation and pneumococcal pneumonia is not well understood. We assessed susceptibility to experimental pneumococcal pneumonia in mice with and without allergic airway inflammation. Susceptibility to pneumococcal pneumonia was evaluated by challenging mice with a bioluminescent Streptococcus pneumoniae strain after sensitization with ovalbumin (OVA), with subsequent monitoring of pneumococcal infection using real-time photonic imaging. Of 46 OVAsensitized mice challenged with pneumococci, 13 (28%) developed imaging findings consistent with pneumococcal pneumonia. In comparison, 28 (57%) of 49 non-sensitized control mice developed pneumococcal pneumonia (P = 0·005). While none of the control group developed meningitis (0%, none of 28), two mice in the OVA-sensitized group developed meningitis (15·4%, two of 13) (P = 0·09). The mean bacterial count in the lung was significantly lower in the OVA-sensitized than the non-sensitized group (8·26 Ϯ 0·69 versus 9·21 Ϯ 0·67 log10 colony-forming units (CFU)/g, P = 0·002). There was a trend towards the mean bacterial count in the spleen being higher in the OVAsensitized versus the non-sensitized group (8·14 Ϯ 0·89 versus 7·45 Ϯ 1·07 log10 CFU/g, P = 0·071). A high level of interleukin (IL)-4 in lung homogenates was associated with risk of pneumococcal infection independent of sensitization with OVA (odds ratio: 49·7, 95% confidence interval 2·92-846·5, per increment of 1·0 pg/ml). In the murine model studied, acute allergic airway inflammation reduced susceptibility to pneumococcal pneumonia. IL-4 may increase the risk of pneumococcal pneumonia independently of allergic airway inflammation.

Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

“…OVA sensitization and challenge decreased the numbers of airway neutrophils, decreased lung IL-6 and IL-1␤ expression, and increased the Pseudomonas aeruginosa lung burden at 24 h postinfection (66). Two groups induced Streptococcus pneumoniae lung infection in the context of antecedent OVA sensitization and challenge (68,69). In experiments with a serotype 4 strain of S. pneumoniae, OVA-induced allergic airway inflammation neither enhanced nor impaired lung bacterial clearance or postinfection mortality (69).…”

“…As asthma and allergic airway inflammation are generally thought to increase risk for invasive bacterial infection and pneumonia in humans (63)(64)(65), several groups have determined the effect of allergic airway inflammation induced by OVA sensitization and challenge in mouse models of lung bacterial infection (66)(67)(68)(69). IL-4 and IL-13 expressed during OVA-induced allergic airway inflammation impaired the lung clearance of Mycoplasma pneumoniae by impairing lung IL-6 and Toll-like receptor 2 expression (67).…”

“…Alternately, using a bioluminescent serotype 3 S. pneumoniae strain, a different group showed that OVA-sensitized and -challenged mice had a decreased frequency of development of pneumonia and a decreased lung bacterial burden at the time of pneumonia onset compared to non-OVA-sensitized mice (68). Thus, OVA sensitization and challenge have different influences on lung bacterial infection depending on the model pathogen used.…”

Mouse Eosinophils Possess Potent Antibacterial Properties In Vivo

“…It should be noted that other studies have demonstrated that the hypereosinophilic state induced by ovalbumin sensitization impairs Pseudomonas clearance in the lung (7). This apparent discrepancy is likely due to the induction of multiple Th2 cytokines in the ovalbumin model, including IL-4, which has recently been shown to promote bacterial growth in vivo (20,23).…”

Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased Expression of Transforming Growth Factor β1 and SiglecF low Alveolar Macrophages

“…The impact of ALI on pulmonary bacterial infections was investigated previously utilizing multiple mouse models, with differing results. Employing in vivo bioluminescent imaging, it was found that ALI reduced the level of pneumococcal burden in the lung, although there was a trend toward enhanced bacterial invasiveness (30). In a pulmonary Pseudomonas infection model, it was reported that OVA sensitization and challenge inhibited antibacterial defenses (31).…”